rs281864955
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_024312.5(GNPTAB):βc.441delβ(p.Asn148ThrfsTer4) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000991 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. A147A) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_024312.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNPTAB | NM_024312.5 | c.441del | p.Asn148ThrfsTer4 | frameshift_variant | 5/21 | ENST00000299314.12 | |
GNPTAB | XM_011538731.3 | c.360del | p.Asn121ThrfsTer4 | frameshift_variant | 5/21 | ||
GNPTAB | XM_006719593.4 | c.441del | p.Asn148ThrfsTer4 | frameshift_variant | 5/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNPTAB | ENST00000299314.12 | c.441del | p.Asn148ThrfsTer4 | frameshift_variant | 5/21 | 1 | NM_024312.5 | P1 | |
GNPTAB | ENST00000549940.5 | c.441del | p.Asn148ThrfsTer4 | frameshift_variant | 5/11 | 1 | |||
GNPTAB | ENST00000552681.1 | c.75del | p.Asn26ThrfsTer4 | frameshift_variant | 1/3 | 1 | |||
GNPTAB | ENST00000550352.1 | n.235del | non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251180Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135760
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461798Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727200
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
Pseudo-Hurler polydystrophy;C2673377:Mucolipidosis type II Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2023 | This sequence change creates a premature translational stop signal (p.Asn148Thrfs*4) in the GNPTAB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GNPTAB are known to be pathogenic (PMID: 19617216, 25107912). This variant is present in population databases (rs775347677, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with mucolipidosis II (PMID: 19659762). ClinVar contains an entry for this variant (Variation ID: 39079). For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Apr 10, 2018 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 21, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 29, 2023 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32651481, 30882951, 19659762) - |
Mucolipidosis type II Pathogenic:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Jul 09, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at